Asymmetric reduction of ketones to form optically active alcohols

ABSTRACT

A process for producing optically active secondary alcohols by reducing an optically inactive ketone in the presence of an optically active Group VIII metal coordination complex catalyst is disclosed. One embodiment is directed to a process for forming optically active aliphatic or aromatic secondary alcohols by reacting an optically inactive ketone with hydrogen in the presence of a Group VIII metal complex catalyst which contains the metal in combination with at least one optically active phosphine or arsine ligand.

United States Patent [1 1 Solodar [451 May 13,1975

1 1 ASYMMETRIC REDUCTION OF KETONES TO FORM OPTICALLY ACTIVE ALCOHOLS [75] Inventor: Arthur John Solodar, St. Louis, Mo.

[73] Assignee: Monsanto Company, St. Louis, Mo.

[22] Filed: Feb. 9, 1972 [21] Appl. No.: 224,971

[52] US. Cl... 260/482 C; 260/570.6 R; 260/584 R; 260/613 D; 260/617 C; 260/618 H; 260/618 D; 260/618 B; 260/633; 260/638 B; 252/430 [51] Int. Cl. C07c 125/04; C07c 29/16 [58] Field of Search 260/617 C, 618 R, 618 D, 260/618 B, 613 D, 638 B [56] References Cited FOREIGN PATENTS OR APPLICATIONS 1,138,601 1/1969 United Kingdom 260/617 C Primary ExaminerLorraine A Weinberger Assistant Examiner-Paul J. Killos [57] ABSTRACT A process for producing optically active secondary alcohols by reducing an optically inactive ketone in the presence of an optically active Group VIII metal coordination complex catalyst is disclosed. One embodiment is directed to a process for forming optically active aliphatic or aromatic secondary alcohols by reacting an optically inactive ketone with hydrogen in the presence of a Group VIII metal complex catalyst which contains the metal in combination with at least one optically active phosphine or arsine ligand.

19 Claims, No Drawings BACKGROUND OF THE INVENTION DESCRIPTION OF THE PREFERRED EMBODIMENTS Secondary alcohols prepared by the process of this An asymmetric carbon atom by commonly accepted 5 invention have the formula definition is a carbon atom containing four different radicals or atoms attached to it. Compounds containing one or more asymmetric carbon atoms are optically active. The carbon atom of the carbonyl group in a ketone cannot be asymmetric because of the doubly bonded oxygen atom attached to it. Even if the two R groups of the ketone compound are different, the carbon atom of the carbonyl group can only contain three different groups, the R, R and the doubly bonded oxygen, and cannot be asymmetric When the ketone is reduced to the secondary alcohol,

I R CH- R SUMMARY OF THE INVENTION Providing a means for producing a preponderance of a desired optical isomer of a secondary alcohol directly from the ketone without the necessity of employing any separation step in addition to the ketone reduction constitutes a principal object of this invention.

This invention relates to a method for preparing optically active secondary alcohols. Specifically, the invention relates to a method for preparing optically active secondary alcohols comprising reacting an optically inactive ketone having no asymmetric atoms of the formula where R is different from R' and where both R's can be any monovalent hydrocarbon group attached directly to the carbonyl group through a carbon atom, with hydrogen in the presence of an optically active catalyst which is a coordination complex comprising a. a Group VIII metal having an atomic number greater than 43, in combination with b. at least one optically active phosphine or arsine ligand.

OH 2 =1= 3 R -C H-R where R and R are different from each other and are any monovalent hydrocarbon group attached directly to the optically active carbon atom through a carbon to carbon bond, and where the indicates the asymmetric carbon atom. The R groups of both the ketone and the alcohol can be either substituted or unsubstituted hydrocarbon groups. If substituted, the substituent groups can be halogen, amino, nitro, hydroxyl, carboxyl and cyano; phosphorus, arsenic, silicon, oxygen and sulfur atoms or groups containing said atoms; and any of a large number of other substituents recognized as capable of being present on hydrocarbon groups. Since the hydrogenation reaction which produces the alcohol acts upon the carbonyl group of the ketone, the R groups can actually be any substituted or unsubstituted hydrocarbon groups which do not interfere with the hydrogenation of the carbonyl group. The above mentioned substituent groups should therefore be considered merely as exemplary and not in any way as limiting the scope of the invention. Examples of secondary alcohols which can be prepared include 2-butanol; 2-octanol; 3-octanol; a-methylbenzylalcohol; a-phenyl-4- chlorobenzyl alcohol; l-amino-3-phenyl-2-propanol; l-chloro-4-methyl-3-pentanol; l-nitro-2-propanol; l-

phenyl-Z-propanol; l-amino-Z-octanol; 2- methylamino-1-(3 -hydroxyphenyl)-ethanol; 3-( 2 methoxyphenoxyl)-propane-l ,2-diol', lisopropylamino-3-( l -naphthoxy)-2-propanol; o-

tolylphenylmethanol; l-carbamoyloxy-3-(2-methoxy phenoxy)-2-propanol; and l-carbamoyloxy-3-(4'- chlorophenoxy)-2-propanol.

The ketones which are hydrogenated to produce secondary alcohols have the formula where the Rs are as described above in connection with the alcohols. In many instances, the R groups of the ketone will correspond exactly with the R groups of the secondary alcohol produced from the ketone. In other instances, the R groups of the ketone may differ from those of the alcohol produced therefrom due to the alteration of the ketone R groups during the hydrogenation reaction. As an example, a ketone R group such as -CI-I=CH could be reduced by the hydrogenation reaction to form a -CI-I CH group on the secondary alcohol. The R groups of the ketones used in this invention are further limited to groups containing no asymmetric atoms. Hence the process of this invention provides asymmetry in a product produced from a starting reactant which contains no asymmetry. Moreover, not only does the product contain a point of asymmetry, but the product is further characterized by a preponderance of one optical isomer over the other.

Examples of suitable ketones include Z-butanone; 2- octanone; 3-octanone; acetophenone; 4- chlorobenzophenone; l-amino-3-phenyl-2-propanone;. t-chloro-4 -methyl-3-pentanone; l-nitro-2-propanone', l-phenyl-Z-propanone; l-amino octanone-2', 2- methylamino-3 '-hydroxyacetophenone; hydroxy-3( 2 methoxyphenoxy)-2-propanone; l isopropylamino-3 (l-naphthoxy)-2-propanone; Z-methylbenzophenone; l-carbamoyloxy-3-(2' methoxyphenoxy)-2- propanone', and l-carbamoyloxy-3(4' chlorophenoxy)-2'propanone.

The production of an optically active alcohol by hydrogenation of a ketone is accomplished through the use of a particular type of catalyst.

The optically active hydrogenation catalysts useful in this invention are coordination complexes comprising a Group VIII metal having an atomic number greater than 43, in combination with at least one optically active phosphine or arsine ligand.

The designation Group VIII refers to Group VIII of the Periodic System of the Elements. The reference to Group VIII metals having an atomic number greater than 43 is used to include ruthenium, rhodium, palladium, osmium, iridium and platinum. Preferred among the foregoing metals are ruthenium, rhodium and iridium, and most preferably rhodium. Mixtures of the foregoing metals in complex form are also useful.

The phosphine or arsine ligand can be of the formula ARR R wherein A is phosphorus or arsenic and R, R and R can be hydrogen, alkyl, aryl, aralkyl, alkaryl, alkoxy, aryloxy, pyrryl, thienyl, furyl, pyridyl, piperidyl, 3-cholesteryl and other similar groups having a maximum of about 12 carbon atoms, groups such as the above which are substituted with other groups such as amino, nitro, carbonyl, carboxyl, halogen, alkoxy and aryloxy preferably having a maximum of about 4 carbon atoms.

Specific examples of substituents on the phosphorus and arsenic atoms include but are not limited to: methyl, ethyl, propyl, isopropyl, butyl and its isomers, pentyl and its isomers, hexyl and its isomers, heptyl and its isomers, octyl and its isomers, nonyl and its isomers, decyl and its isomers, undecyl and its isomers, dodecyl and its isomers, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, acetoxylphenyl, methylphenyl, ethylphenyl, propylphenyl, butylphenyl, dimethyl phenyl, trimethylphenyl, diethylphenyl, hydroxyphenyl, phenoxyphenyl, o-anisyl, 3-cholesteryl, benzyl, pyrrl, furyl, pyridyl, thienyl, piperidyl, menthyl, bornyl and pinyl.

A list of optically active phosphine and arsines which may be utilized includes but is not limited to: methylethylphosphine, rnethylisopropylphosphine, ethylbutylphosphine, isopropylisobutylphosphine, methylphenylphosphine, ethylphenylphosphine, propylphenylphosphine, butylphenylphosphine, phenylbenzylphosphine, phenylpyrrolephosphine, ethylisopropylisobutylphosphine, methylphenyl-4-methylphenylphosphine, ethylphenyl-4-methylphenylphosphine, methylisopropyl phenylphosphine ethylphenyl-2,4,S-trimethylphenylphosphine, phenylbenzyl-4-dimethylaminophenylphosphine, phenylpyridylmethylphosphine, phenylcyclope' ntylethylphosphine, cyclohexylmethylisopropylphosphine, o-rnethoxyphenylmethylphenylphosphine, omethoxyphenylcyclohexylmethylphosphine and the arsenic analogs of the above.

Examples of suitable ligands that are useful in making catalysts in the present invention include optically active phosphines and arsines containing at least one phenyl group that has a substituent in the ortho position such as hydroxy', alkoxy having at least one carbon atom and a maximum of l2 carbon atoms; and aryloxy. Good results have been obtained with methylphenyl-oanisylphosphine and methylcyclohexyl-oanisylphosphine as ligands.

Optical activity of the metal coordination complexes of this invention resides in the phosphine or arsine ligand. This optical activity may result either from having three different groups on the phosphorus or arsenic atom or by having an optically active group attached to the phosphorus or arsenic atom. Although only one optically active group or ligand is required in the coordination metal complex catalyst, it is preferred, for ease of preparation, that all ligands of the types described below be the same.

Illustrative coordination metal complexes can be represented by the formula MX L or M X L wherein M is rhodium, iridium, ruthenium or osmium; M is palladium or platinum; X is hydrogen or halogen, L is the phosphine or arsine ligand as previously defined and n is the integer one or three.

In the above coordination metal complex formulae, only one ligand (L) has to be optically active in order for the process of the reaction to be operable. If the op tical activity of the ligand resides in having an optically active group attached to the phosphorus or arsenic atom, there only has to be one such group, and the other two groups may be the same or inactive. In this instance, only one of the groups R, R or R has to be optically active, the remaining two groups may be identical or inactive.

Catalysts which may be used include, but are not limited to, coordination metal complexes of the following formulae. In the formulae, an asterisk indicates asymmetry, and therefore optical activity. The asterisk denotes the asymmetric atom or disymmetric group. An an example: A indicates the phosphorus or arsenic is asymmetric. Absence of an asterisk indicates no optical activity.

xvi. M X (AR* R R) (AR R R where M, M X, A, R, R and R' are as previously defined.

It is understood that in the above illustrated list of catalysts, the dissymmetric group can be R, R or R and is not restricted to any one group. In addition, there may be a combination of moieties attached to the metal.

It should be understood that the above described formulae represent not only the coordination metal complexes that contain two or three ligands, as in the formulae M X L or M X,,L respectively, but also represent those coordination metal complexes wherein the number of ligand-metal coordination bonds are described by the number of L's in the formula and wherein these bonds are provided by polydentate type ligands. For instance, although there may be only two ligands in a particular coordination metal complex, the formula M X L still represents the complex if one of the two ligands is bidentate, i.e., it provides two coordination bonds. Likewise the formula M'X L aiso represents those complexes wherein there is only one ligand present if that ligand is tridentate, i.e., it provides three coordination bonds.

Catalysts which are soluble in the starting reactants or some suitable solvent which can be used with the starting reactants are referred to as homogeneous cata lysts and constitute one preferred embodiment of this invention. Another form of catalyst useful herein is bonded to some non-soluble phase such as an ionexchange resin, which is then contacted with the ke tone reactant, thereby providing the necessary thor ough contact between catalyst and reactants.

It has been found that excellent yields of desired enantiomorphs can be achieved not only with the above described optically active hydrogenation catalysts. but can also be achieved when the hydrogenation is carried out in the presence of a catalyst that comprises a solution of a metal compound where the metallic component is rhodium, iridium, ruthenium, osmium, palladium or platinum, and at least one equivalent of a phosphine and/or arsine ligand per mole of metal, provided that the ligand is optically active. For instance, the catalyst can be prepared in situ by dissolving a soluble metal compound in a suitable solvent together with a ligand wherein the ratio of ligand to metal is at least one equivalent of ligand per mole of metal, preferably two equivalents of ligand per mole of metal. Likewise, it has been found that the catalyst can be formed in situ by adding a soluble metal compound to the reaction mass together with the addition of the proper amount of the optically active ligand to the reaction mass either before or during hydrogenation.

The preferred metal used herein is rhodium. Solubie rhodium compounds that can be utilized include rhodium trichloride hydrate, rhodium tribrornide hydrate, rhodium sulfate, organic rhodium complexes with eth ylene, propylene, etc., and his olefins such as 1,5- cyclooctadiene and 1,5-hexadiene, bicycIo-[2.2.l 1- hepta-2,5-diene and other dienes which can form bidentate ligands, or an active form of metallic rhodium that is readily solubilized.

Cationic coordination metal complexes containing two equivalents of phosphine or arsine per mole of metal and a chelating bis-olefin can be used as the catalysts in the present invention. For instance, using the organic rhodium complexes, as described above, one can prepare such cationic coordination rhodium complexes by slurrying the organic rhodium complex in an alcohol, such as ethanol, adding two equivaients of the optically active phosphinc or arsine so that an ionic solution is formed followed by the addition of a suitable anion such as, for instance, tetrafluoroborate, tetraphenylborate or any other anion that will resuit in the precipitation or crystallization of a solid cationic coordination metal complex either directly from the solution or upon treatment in an appropriate solvent.

For instance, exemplary cationic coordination metal complexes are l,5-cyclooctadienebis(methylcyclohexyl-o-anisylphosphine) rhodium tetrafluoroborate, 1,5-cyclooctadienebis(methylcyclohexyl oanisylphosphine) rhodium tetraphenylborate and bicycle-[2.2.1]hepta-2.5-dienebis(methylcyclohexyl-o-anisylphosphine) rhodium tetrafluoroborate.

Without prejudice to the present invention it is thought that the charged components, referred to here inabove as catalysts, are actually catalyst precursors and that upon contact with hydrogen the precursors are converted to an active catalystic form. This conversion can, of course, be carried out during the actual hydro genation of the ketone or can be accomplished by subjecting the catalyst (or precursor) to hydrogen prior to addition to the ketone material to be hydrogenated,

The hydrogenation reaction is usually conducted in a solvent, such as benzene, ethanol, toluene, cyclohex ane, and mixtures of these solvents. Almost any aro matic or saturated alkane or cycloalkane solvent, which is inactive to the hydrogenation conditions of this reaction, can be used. Carboxylic acids, esters, anhydrides, amides, and ethers can also be employed. Since the hydrogenation process of this invention has been found to be specific, solvents such as nitrobenzene can also be utilized. Preferred solvents are alcohols such as methanol or ethanol, and carboxylic acids such as acetic acid. Alternatively, the reaction can be carried out using only neat reactants.

The catalyst can be added to the solvent or reactants either as a compound per se or as its components which then form the catalyst in situ. When the catalyst is added as its components it may be added prior to, or at the same time as, the ketone. Components for the preparation of the catalyst in situ are the soluble metal compound and the optically active phosphine or arsine ligand. The catalyst can be added in any effective cata lytic amount and generally in the range of about 0.000! to about 5 percent by weight of contained metal based on the ketone reactant. A preferred concentration range is from about 0.0002 to about 0.2 percent of the ketone.

it has been found that the process of this invention is preferably carried out in the presence of an optically active phosphine or arsine ligand wherein the ligand is present in a ratio of about 1.0 or less up to about 200 or more equivalents of ligand per mole of metal, although the range of about 1.5 to about 2.9 and more preferably about 2.0 equivalents, has been found to be especially useful. In practice, it is preferred to have the optically active catalyst in a solid form for purposes of handiing and storage. It has been found that these results can be obtained with solid, cationic coordination metal complexes.

Within practical limits, means should be provided so as to avoid contacting the catalyst or reaction mass with oxidizing materials. In particular, care should be taken so as to avoid contact with oxygen. It is preferred to carry out the hydrogenation reaction preparation and actual reaction in gases (other than H that are inert to both reactants and catalysts such as, for instance, nitrogen or carbon dioxide,

After addition of the components to the solvent, hydrogen is added to the mixture until about 1 to about times the mole quantity of the ketone or an amount necessary to complete the hydrogenation to the point desired has been added. The pressure of the system will necessarily vary since it will be dependent upon the type of ketone, type of catalyst, size of hydrogenation apparatus, amount of components and amount of solvent. Lower pressures, including atmospheric and subatmospheric pressure, can be used as well as higher pressures. Examples set forth below have used pres sures in the range of about 3 to 7 atmospheres, although pressures as high as 40 to 50 atmospheres can be used.

Reaction temperatures may be in the range of about 20 to about 1 10C. Higher temperatures may be used but are normally not required and may lead to an increase of side reactions such as the racemization of the optically active ligands. Preferred temperatures are about 40 to 100C.

One additive sometimes used in the hydrogenation reaction is water. A small amount of water in the range of 1 percent or less of the reactants acts as a rate accelerator and can therefore be useful in the practice ofthis invention. It has been found, however, that the presence of water may reduce the optical purity of the alcohol product. That is, the catalyzed hydrogenation reaction of this invention, if carried out under anhydrous conditions, may produce alcohols with a greater optical purity than is obtained when small amounts of water are present. It has been found that as little as 0.05 percent water has the above-mentioned effects on reaction rate and product optical purity.

Upon completion of the reaction which is determined by conventional means, the solvent is removed and the products and catalysts separated by conventional means.

Many naturally occurring products and medicaments exist in an optically active form. In these cases only one of the L or D forms is usually effective. Synthetic preparation of these compounds in the past has required an additional step of separating the products into its enan tiomorphs. This process is expensive and time consuming. The process of the present invention permits the formation of optically active products thus eliminating much of the time consuming and expensive separation of enantiomorphs while improving the yield of desired enantiomorphs and reducing the yield of unwanted enantiomorphs.

The following examples are given to illustrate in detail how the process of this invention is carried out. It is to be understood that the specific details given in the examples are not to be construed as limiting the scope of the invention. In the following examples parts are by weight unless otherwise indicated. In the examples the percent optical purity is determined by the following equation (it is understood that the optical activities expressed as the specific rotations are measured in the same solvent):

Percent Optical Purity (observed optical activity of the mixture X 100)/optical activity of pure enantiomorph EXAMPLE 1 Into a 3-ounce glass pressure bottle are placed 66.4 milligrams of [Rh(norbornadiene)Cl] 98 milligrams of optically active phenylmethyliso-propylphosphine (b11 +1 1.0 [to1uene, c O.50]), 8.2 grams of 2- octanone and 0.1 ml water. The bottle is flushed by filling 4 times for at least 30 seconds with at least 30 psig hydrogen and then venting the gas and is then filled to 30 psig hydrogen. The bottle is warmed to 60C and the contents stirred for 21 hours. The reaction mass is dis tilled to afford a mixture of 2-octanone and 2-octanol. The Z-octanol has {011 0.60, optical purity 5.9 percent.

EXAMPLE 2 Into a 3-ounce glass pressure bottle are placed 49 milligrams of [Rh( 1,5-cyclooctadiene) (oanisylcyclohexylmethylphosphine ]BF (optical purity of phosphine -95 percent), 8.2 grams of 2-octanone, 0.20 ml water, and 10 ml iso-butyric acid. The bottle is flushed 4 times as in Example 1 and then filled to psig hydrogen. The bottle is warmed to 72C and the contents stirred for 19.5 hours. The reaction solution is then dissolved in 50 ml chloroform, washed 3 times with 50 ml 5 percent aqueous sodium hydroxide solution and once with 20 ml water and then dried with anhydrous magnesium sulfate. Distillation affords a mixture of 2-octanol and 2-octanone. The 2-octanol has [M l.148, optical purity 11.2 percent.

EXAMPLE 3 Into a 3-ounce glass pressure bottle are placed 1.15 grams C H COCH NHCH C H 18 milligrams of [Rh( 1 ,S-cyclooctadiene) (o-anisylcyclohexylmethylphosphineMBF. (phosphine optical purity percent), 20 ml absolute ethanol and 0.20 ml water. The bottle is flushed and filled as in Example 1 with 60 psig hydrogen. The bottle is warmed to 55C and the contents stirred for 3.25 hours. The solvent is removed by distillation and the product, C H CHOHCH NHCl-l C l-l isolated by extraction into hot hexane and crystallization from cold hexane. [t has [M -1 .7 (absolute EtOH, c 0.66).

EXAMPLE 4 Into a 3-ounce glass pressure bottle are placed 173 milligrams of [Rh(norbornadiene) (iso-propylmethylpl1enylphosphine) ]BF.,([01],, +11.0 for the phosphine), 8.2 grams of 2-octanone, 5 ml absolute ethanol, and 0.12 ml water. The bottle is flushed and filled with hydrogen as in Example 1 to 43 psig hydrogen. The bottle is warmed to 75C and the contents stirred for 3.5 hours. The reaction mass is distilled to afford almost pure 2-octano1, (011 +0.15, optical purity 1.5 percent.

EXAMPLE 5 Into a 3-ounce glass pressure bottle are placed 75 milligrams of [Rh(norbornadiene)Cl} 7.7 grams of acetophenone, 2 m1 absolute ethanol, 113 milligrams iso-propylphenylmethylphosphine ([01],, +11.0) and 0.12 ml water. The bottle is flushed and filled with hydrogen as in Example 1 to 30 psig hydrogen. The bottle is warmed to 60C and the contents stirred for 43 hours. Distillation of the reaction mass affords a mixture of acetophenone and a-methylbenzyl alcohol. The a-methylbenzyl alcohol has [11],, +4.87", optical purity 1 1.4 percent.

EXAMPLE 6 Into 8 3-ounce glass pressure bottle are placed 180 milligrams of [Rh(norbornadiene) (iso-propylphenylmethylphosphineMBF, ([11],, +1 1.0 for the phosphine), 7.7 grams of acetophenone, 3 ml absolute ethanol, and 0.12 ml water. The bottle is flushed and filled with hydrogen as in Example 1 to 30 psig. The bottle is warmed to 60C and the contents stirred for 5 hours. Distillation of the reaction mass affords pure a-methylbenzyl alcohol, [011 l.78, optical purity 4.2 percent.

EXAMPLE 7 Into a 3-ounce glass pressure bottle are placed 73.6 milligrams of [Rh(norbornadiene)Cl] 178 milligrams of phenylmethyl n-decylphosphine (optical purity 76 percent), 7.7 grams of acetophenone, 2 ml absolute ethanol, and 0.12 ml water. The bottle is flushed and filled with hydrogen as in Example 1 to 30 psig. The bottle is warmed to 65C and the contents stirred for 18 hours. The reaction mass is distilled to afford a mixture of acetophenone, and a-methylbenzyl alcohol. The a-methylbenzyl alcohol has [a] =+l.47, optical purity 3.5 percent.

EXAMPLE 8 Into a 3-ounce glass pressure bottle are placed 49 milligrams of [Rh( 1,5-cyclooctadiene) (oanisylcyclohexylmethylphosphine) BF (phosphine optical purity -95 percent), 10.2 grams phenylacetone and 10 ml iso-butyric acid. The bottle is flushed by filling 4 times for at least 30 seconds with at least 30 psig hydrogen, followed by venting the gas and a final fiiling with hydrogen to 70 psig. The bottle is warmed to 80C and stirred for 24 hours. The reaction mass is dissolved in 50 ml chloroform, washed three times with 50 ml 5 percent aqueous sodium hydroxide solution, once with ml water and then dried over anhydrous magnesium sulfate. Distillation affords a mixture of l-phenyl-"- propanol and phenylacetone. The l-phenyl-Z-propanol has [011 -5.3l, optical purity 19.9 percent.

What is claimed is:

l. A process for preparing an optically active secon dary alcohol comprising reacting an optically inactive ketone having no asymmetric atoms of the formula where R is different from R and where both Rs can be any substituted or unsubstituted monovalent hydrocarbon group attached directly to the carbonyl group through a carbon atom, with hydrogen in the presence of an optically active catalyst which is a coordination complex comprising a. a Group VIII metal having an atomic number greater than 43, in combination with b. at least one optically active phosphine or arsine ii gand wherein the optical activity results from having three different groups bonded to the phosphine or arsine atom. 2. A process according to claim 1 where the Group VIII metal is ruthenium, rhodium or iridium.

3. A process according to claim 1 where the Group Vlll metal is rhodium.

4. A process according to claim 1 wherein at least one of said optically active ligands is a phosphine ligand.

5. A process according to claim I wherein all of said ligand is a phosphine ligand.

6. A process according to claim 1 wherein the ratio of optically active phosphine or arsine ligand is from about 1.5 to about 2.9 equivalents of ligand per mole of said Group VIII metal.

7. A process according to claim 6 wherein said Group VIII metal is ruthenium, rhodium or iridium.

8. A process according to claim 6 wherein said Group Vlll metal is the metallic component in a coordination metal complex containing two equivalents of phosphinc or arsine ligand per mole of metal.

9. A process according to claim 8 wherein said optically active catalyst contains two olefinic ligands per mole of metal in addition to the two phosphine or arsine ligands.

10. A process according to claim 1 wherein said optically active catalyst is formed in situ.

11. A process according to claim 1 wherein said optically active catalyst is a coordination complex of the formula b. M X L where M is rhodium, ruthenium. iridium or osmium; M is palladium or platinum; X is hydrogen or halogen; n is the integer l or 3; and L is a phosphine or arsine ligand, provided that at least one L group is optically active.

12. A process according to claim 1 wherein said opticaily active catalyst is a solution of said Group VIII metal and said ligand.

13. A process according to claim 1 wherein the R groups of said ketone are substituted monovalent hydrocarbn groups.

14. A process according to claim 1 wherein said optically active secondary alcohol is 2-methylamino-1-(3'- hydroxyphenyll-ethanol.

15. A process according to claim 1 wherein said optically active secondary alcohol is 3-( 2 methoxyphenoxy )-propane-l ,2-diol.

16. A process according to claim 1 wherein said opti cally active secondary alcohol is l-isopropy1amino-3- (1'-naphthoxy)-2-propanol.

17. A process according to claim 1 wherein said optically active secondary alcohol is otolyiphenylmethanol.

18. A process according to claim 1 wherein said optically active secondary alcohol is l-carbamoyloxy-Il- (2'-methoxyphenoxy)-2-propan0l.

19. A process according to ciaim 1 wherein said optically active secondary alcohol is lcarbamoyloxy 3- (4-chlorophenoxy)-2propanol. 

1. A PROCESS FOR PREPARING AN OPTICALLY ACTIVE SECONDARY ALCOHOL COMPRISING REACTING AN OPTICALLY INACTIVE KETONE HAVING NO ASYMMETRIC ATOMS OF THE FORMULA
 2. A process according to claim 1 where the Group VIII metal is ruthenium, rhodium or iridium.
 3. A process according to claim 1 where the Group VIII metal is rhodium.
 4. A process according to claim 1 wherein at least one of said optically active ligands is a phosphine ligand.
 5. A process according to claim 1 wherein all of said ligand is a phosphine ligand.
 6. A process according to claim 1 wherein the ratio of optically active phosphine or arsine ligand is from about 1.5 to about 2.9 eqUivalents of ligand per mole of said Group VIII metal.
 7. A process according to claim 6 wherein said Group VIII metal is ruthenium, rhodium or iridium.
 8. A process according to claim 6 wherein said Group VIII metal is the metallic component in a coordination metal complex containing two equivalents of phosphine or arsine ligand per mole of metal.
 9. A process according to claim 8 wherein said optically active catalyst contains two olefinic ligands per mole of metal in addition to the two phosphine or arsine ligands.
 10. A process according to claim 1 wherein said optically active catalyst is formed in situ.
 11. A process according to claim 1 wherein said optically active catalyst is a coordination complex of the formula a. M1XnL3 or b. M2X2L2 where M1 is rhodium, ruthenium, iridium or osmium; M2 is palladium or platinum; X is hydrogen or halogen; n is the integer 1 or 3; and L is a phosphine or arsine ligand, provided that at least one L group is optically active.
 12. A process according to claim 1 wherein said optically active catalyst is a solution of said Group VIII metal and said ligand.
 13. A process according to claim 1 wherein the R groups of said ketone are substituted monovalent hydrocarbn groups.
 14. A process according to claim 1 wherein said optically active secondary alcohol is 2-methylamino-1-(3''-hydroxyphenyl)-ethanol.
 15. A process according to claim 1 wherein said optically active secondary alcohol is 3-(2''-methoxyphenoxy)-propane-1,2-diol.
 16. A process according to claim 1 wherein said optically active secondary alcohol is 1-isopropylamino-3-(1''-naphthoxy)-2-propanol.
 17. A process according to claim 1 wherein said optically active secondary alcohol is o-tolylphenylmethanol.
 18. A process according to claim 1 wherein said optically active secondary alcohol is 1-carbamoyloxy-3-(2''-methoxyphenoxy)-2-propanol.
 19. A process according to claim 1 wherein said optically active secondary alcohol is 1-carbamoyloxy-3-(4''-chlorophenoxy)-2-propanol. 